Clinical and Translational Research
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Surg. Mar 27, 2024; 16(3): 842-859
Published online Mar 27, 2024. doi: 10.4240/wjgs.v16.i3.842
Construction and validation of somatic mutation-derived long non-coding RNAs signatures of genomic instability to predict prognosis of hepatocellular carcinoma
Bo-Tao Duan, Xue-Kai Zhao, Yang-Yang Cui, De-Zheng Liu, Lin Wang, Lei Zhou, Xing-Yuan Zhang
Bo-Tao Duan, Xue-Kai Zhao, Yang-Yang Cui, De-Zheng Liu, Lei Zhou, Xing-Yuan Zhang, Department of Hepatobiliary Surgery, Binzhou Medical University Hospital, Binzhou 256600, Shandong Province, China
Lin Wang, Department of Ophthalmology, Binzhou Medical University Hospital, Binzhou 256600, Shandong Province, China
Co-first authors: Bo-Tao Duan and Xue-Kai Zhao.
Author contributions: Duan BT and Zhao XK drafted the manuscript; Zhou L and Zhang XY provided guiding advice on manuscript editing. All authors approved the final version of the manuscript.
Institutional review board statement: No human or animal research was included in this study.
Clinical trial registration statement: This study is a bioinformatics article and does not involve clinical trials. There are no relevant participants involved.
Informed consent statement: No human research was included in this study.
Conflict-of-interest statement: The authors declare that they have no competing interests.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Lei Zhou, MD, Full Professor, Department of Hepatobiliary Surgery, Binzhou Medical University Hospital, No. 661 Huanghe 2nd Road, Binzhou 256600, Shandong Province, China. dr_zhlei@163.com
Received: October 2, 2023
Peer-review started: October 2, 2023
First decision: December 8, 2023
Revised: December 20, 2023
Accepted: February 19, 2024
Article in press: February 19, 2024
Published online: March 27, 2024
Processing time: 171 Days and 19.9 Hours
ARTICLE HIGHLIGHTS
Research background

Long stranded non coding RNA (LncRNA) has been found to be a potential prognostic factor in cancer, including hepatocellular carcinoma (HCC). Some LncRNAs have been confirmed as potential indicators for quantifying genomic instability (GI). However, GI-LncRNAs have yet to be largely explored. This study established the GI-derived LncRNA signature (GILncSig), which can predict the prognosis of HCC patients.

Research motivation

We established a GILncSig that can predict the prognosis of HCC patients, which can help to guide prognostic evaluation and treatment decisions.

Research objectives

The aim of this study was to establish a GILncSig for predicting the prognosis of HCC patients. At present, the treatment of liver cancer has achieved certain results. However, existing research evidence suggests that the treatment options currently used in clinical practice are still relatively ineffective. The objective effective rate of treatment is still largely inadequate, and most patients do not have good responses. The 5-year overall survival of metastatic HCC is still not ideal. Further research should mainly focus on expanding treatment targets and searching for reliable biomarkers, which will help adjust treatment choices and avoid the risks and costs associated with drug ineffectiveness and side effects. Therefore, there is an urgent need for new biomarkers to predict the prognosis of HCC patients.

Research methods

GI-LncRNAs were identified by combining LncRNA expression and somatic mutation profiles. Next, GI-LncRNAs were analyzed for functional enrichment. The GILncSig was established in the training set by Cox regression analysis, and its predictive ability was verified in the testing set and TCGA set. In addition, we explored the effects of the GILncSig and TP53 on prognosis.

Research results

A total of 88 GI-LncRNAs were found, and functional enrichment analysis showed that their functions were mainly involved in small molecule metabolism and GI. The GILncSig was constructed by 5 LncRNAs (miR210HG, AC016735.1, AC116351.1, AC010643.1, LUCAT1). In the training set, the prognosis of high-risk patients was significantly worse than that of low-risk patients, and similar results were verified in the testing set and TCGA set. Multivariate Cox regression analysis and stratified analysis confirmed that the GILncSig could be used as an independent prognostic factor. ROC curve analysis of the GILncSig showed that its area under the curve (0.773) was higher than the two LncRNA signatures published recently. Furthermore, the GILncSig may have a better predictive performance than TP53 mutation status alone.

Research conclusions

We established a GILncSig that can predict the prognosis of HCC patients, which will help to guide prognostic evaluation and treatment decisions.

Research perspectives

It is necessary to find new reliable biomarkers to predict the prognosis of HCC patients, adjust the treatment plan, and avoid the risks and costs associated with drug ineffectiveness and side effects.